Pharmaceutical Composition For The Parenteral Administration Of Ultrashort-Effective Beta-Adrenoreceptor Antagonists

Abstract

The present invention relates to a pharmaceutical composition in the form of a storage-stable solution for the parenteral administration of ultrashort-effective β-adrenoreceptor antagonists, comprising a) an ultrashort-effective β-adrenoreceptor antagonist and/or a pharmaceutically acceptable salt thereof, b) water, and c) a cyclodextrin and/or a functional cyclodextrin derivative. The composition according to the invention has high stability, even without the presence of additional adjuvants.

1 - 12 . (canceled) 
     
     
         13 . A pharmaceutical composition comprising:
 a) an ultrashort-effective β-adrenoreceptor antagonist or a pharmaceutically acceptable salt thereof;   b) water; and   c) a cyclodextrin or a functional cyclodextrin derivative.   
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein the pH value of the composition is 3 to 7.5. 
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein the pH value of the composition is 5 to 7. 
     
     
         16 . The pharmaceutical composition of  claim 13 , wherein the concentration of the cyclodextrin or the functional derivative thereof is 0.1% to 20% (w/v). 
     
     
         17 . The pharmaceutical composition of  claim 16 , wherein, the concentration of the cyclodextrin or the functional derivative thereof is 0.25% to 7% (w/v). 
     
     
         18 . The pharmaceutical composition of  claim 17 , wherein the concentration of the cyclodextrin or the functional derivative thereof is 0.5% to 4%. 
     
     
         19 . The pharmaceutical composition of  claim 13 , wherein the cyclodextrin is selected from the group consisting of α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin. 
     
     
         20 . The pharmaceutical composition of  claim 13 , wherein the functional cyclodextrin derivative is selected from the group consisting of (2-hydroxypropyl)-β-cyclodextrin and (sulfobutylether)-7β-cyclodextrin. 
     
     
         21 . The pharmaceutical composition of  claim 13 , wherein the ultrashort-effective β-adrenoreceptor antagonist is selected from the group consisting of esmolol, landiolol, and flestolol. 
     
     
         22 . The pharmaceutical composition of  claim 13 , wherein the concentration of the ultrashort-effective β-adrenoreceptor antagonist or salt thereof is 0.1% to 30%. 
     
     
         23 . The pharmaceutical composition of  claim 13 , wherein the composition has an osmolarity of 270 mosmol/l to 310 mosmol/l. 
     
     
         24 . The pharmaceutical composition of  claim 23 , wherein the composition has an osmolarity of 280 mosmol/l to 300 mosmol/l. 
     
     
         25 . The pharmaceutical composition of  claim 13 , wherein the ultrashort-effective β-adrenoreceptor antagonist is esmolol or a salt thereof, and further wherein the composition is present in the form of a sales unit selected from the group consisting of:
 1 ml solution containing 10-20 mg esmolol or a salt thereof,   2 ml solution containing 10-100 mg esmolol or a salt thereof,   5 ml solution containing 50-500 mg esmolol or a salt thereof,   10 ml solution containing 50-5000 mg esmolol or a salt thereof,   10 ml solution containing 2500 mg esmolol or a salt thereof,   50 ml solution containing 50-5000 mg esmolol or a salt thereof,   100 ml solution containing 50-5000 mg esmolol or a salt thereof, and   250 ml solution containing 50-5000 mg esmolol or a salt thereof.   
     
     
         26 . The pharmaceutical composition of  claim 13 , wherein the ultrashort-effective β-adrenoreceptor antagonist is landiolol or festolol or a salt thereof, and further wherein the composition is present in the form of a sales unit selected from the group consisting of:
 1 ml solution containing 5-20 mg landiolol or festolol or a salt thereof,   2 ml solution containing 5-100 mg landiolol or festolol or a salt thereof,   5 ml solution containing 10-500 mg landiolol or festolol or a salt thereof,   10 ml solution containing 10-5000 mg landiolol or festolol or a salt thereof,   25 ml solution containing 25-2500 mg landiolol or festolol or a salt thereof,   50 ml solution containing 50-5000 mg landiolol or festolol or a salt thereof,   100 ml solution containing 50-5000 mg landiolol or festolol or a salt thereof, and   250 ml solution containing 50-5000 mg landiolol or festolol or a salt thereof.   
     
     
         27 . A method of reducing heart beat frequency in a patient comprising administering a composition of  claim 13  to a patient, whereby the heart beat frequency in the patient is reduced. 
     
     
         28 . The method of  claim 27 , wherein the patient has atrial fibrillation, atrial flutter, sinus tachycardia, atrioventricular tachycardia, AV node tachycardia, supraventricular tachycardia, ventricular arrhythmias, perioperative ischaemia, unstable angina pectoris, or acute myocardial infarction.